HDCN Article Review/Hyperlink

Ponticelli C, Civati G, Tarantino A, et al.

Randomized study of cyclosporin in kidney transplantation: a 10-year follow up

J Am Soc Nephrol (May) 7:792-797 1996

The objective of this study was to compare the efficacy and toxicity after 10 years of treatment with cyclosporin vs. azathioprine in cadaveric renal transplantation. 108 cadaveric transplant recipients were randomized to receive cyclosporin (n=55) or azathioprine (n=53) both in combination with steroids. The initial azathioprine dose was 3 mg/kg/d and then adjusted to keep WBC count more than 5,000/mm3. Cyclosporin was given at 5 mg/kg IV followed by 15 mg/kg/d p.o. with gradual dosage reductions every 2 weeks. The maintenance dose was then adjusted to keep blood levels of 100-200 ng/ml (monoconal assay). Cyclosporin toxicity was diagnosed by fine-needle biopsy. Statistical analysis was intention-to-treat.

Ten year patient survival was 89% in cyclosporin group and 83% in azathioprine group (pNS). 10-year graft survivals were 56% and 35%, respectively (p=0.009). The rate of early rejection was significantly lower in the cyclosporin group. After 1 year, there was no difference in half- life of functioning grafts, and the decline in graft function after 1 year was similar in the two groups. There were trends for increased cataracts in the cyclosporin group and increased cardiovascular events in the azathioprine group. The conclusion of the study was, that cyclosporin is associated with better long-term graft survival than azathioprine with no increase in toxicity.

Comment: This is a well-done study with important clinical results. The improvement in long-term graft survival with cyclosporin can be attributed to less graft loss during the first year. Some clinicians substitute azathioprine for cyclosporin after the first year in the hope of preventing chronic cyclosporin toxicity and graft loss. These data, as well as those of the Collaborative Transplant Study, do not support this practice. (David J. Leehey, M.D., Loyola University at Chicago)